PennCSER (Penn Center for the Study of Epigenetics in Reproduction) will elucidate epigenetic mechanisms that govern male and female reproduction, contribute to male infertility and impact development of human and mouse embryos and extra-embryonic tissues. The Center's centerpiece is 4 integrated, innovative research projects, spearheaded by experienced leaders. A pilot project from a young investigator (Butts) and a project based on a productive collaboration of our K12/RSDP junior faculty (Mainigi) with the Northwestern SCCPIR are also described. An outreach program that introduces a novel classroom, laboratory and internet-based Reproduction module into an existing and highly successful biology program for high school students in Philadelphia public schools is proposed. Finally, initiation of a training program on the epigenetics of reproduction for trainees from other U54 and K12 programs is described. Core projects: Project I (Coutifaris/Sapienza) will assess the impact of oxygen tension on DNA methylation and gene expression in newborns, extra-embryonic tissues and on trophoblast differentiation and function following IVF pregnancies and pregnancies resulting from unassisted conception. In Project II (Bartolomei/Schultz) a validated mouse model will be used to study the effect of ART procedures, including variable oxygen tensions, on epigenetic gene regulation in midgestation embryos and at term. Behavioral, developmental and physiological outcomes will be evaluated. Project III (Berger) will investigate histone modifications during mouse spermatogenesis and determine their conservation in normal human sperm and disruption in abnormal human sperm and mouse models exhibiting deregulated poly(ADP-ribose) (PAR) metabolism. Project IV (Meyer) will investigate the role of PAR metabolism in establishment, erasure and maintenance of epigenetic marks in the male germline and ascertain whether defects in PAR metabolism are associated with abnormal human sperm. Addition of the Penn Center to the SCCPIR will bring a new and comprehensive level of understanding to the evolving role of epigenetics in reproduction, will broaden the current areas of expertise and investigation of the consortium and will open new avenues of collaboration, education and training.